A pH-Responsive Dual-drug Delivery System Based on Chitosan

Chitosan-doxorubicin prodrug with the linkage of hydrazone bond (Chitosan-hz-DOX) was employed as the carrier ofcamptothecin (CPT) to develop a dual-drugdelivery system (CPT-CS-DOX). UV-Vis, DLS, and TEM analyses were conducted to investigate the diameter, morphology, drug loading and releasebehaviors of the system. With the increase in the grafting content of DOX on chitosan, the resultant Chitosan-hz-DOX prodrug showed an enhanced loading capacity of CPT. The optimal addition amount of CPT to prepare CPT-CS-DOX was determined to be 20%. After loading CPT, the Chitosan-hz-DOX nanoparticles still remained the spherical morphology but their diameters were increased. In addition, the diameter of CPT-CS-DOX was decreased gradually with the DOX content of Chitosan-hz-DOXbecause of the strong hydrophobic interactions. The premature releases of DOX and CPT at pH = 7. 4 were effectively inhibited from the delivery system, that is, their cumulative releases were 10% and 20%, respectively. Compared with that, in particular, their release rates were remarkably increased at acidic conditions, showing a highly pH-dependent drug release behavior. Furthermore, Peppas equation was employed to analyze the release mechanism of DOX and CPT at different environment conditions. Their release process can be divided into two stages. Thereleases of DOX and CPT at the first stagefollowedthe Fick-diffusion controlled and swelling controlled mechanisms at neutral condition, while at acidic conditions, the release mechanism of CPT remained unchanged but that of DOX was changed. At the second stage,the releases of both drugs obeyedtheFick-diffusion controlledmechanism.